The alternative pathway of complement activation provides nonimmune recognition of microorganisms and altered mammalian cells leading to host defense reactions of opsonization, cytolysis, and inflammation. In human serum the alternative pathway can be activated by bacterial and fungal cell wall materials, by virus-infected human cells, and by some mammalian erythrocytes. Although the chemical characteristics required for activation have not been defined, particulate activators share the ability to provide sites for the formation of the alternative pathway C3 convertase which are protected from serum regulatory proteins. Changes in mammalian cell surfaces such as removal of sialic acid from erythrocytes can influence their ability to serve this protective function. We have found that model lipid membranes in the form of liposomes can activate complement by the alternative pathway and that changes in composition affect this ability. Since the composition of the liposomes is defined and easily modified, they provide a simple model with which to study the role of membrane lipids in alternative pathway activation. We propose to use this model to study the influence of particular membrane lipids and glycolipids on the formation and regulation of the C3 convertase. We will determine which lipids provide binding sites for C3 and which interact with the control proteins (Beta1H and C3b inactivator). We will study the role of viral glycoproteins in activation by measles-infected cells by incorporating purified viral and cell membrane glycoproteins into liposomes and measuring alternative pathway activation. These studies will increase our knowledge of the membrane determinants of the alternative pathway recognition system. The findings will add to our understanding of host defense against bacterial and viral infection.